CRYOGLOBULINEMIA & POEMS
SYNDROME
Morie Gertz
Mayo Clinic
Monoclonal Gammopathies
Mayo Clinic
n=31,479 SMM 4% (1,178)
Lymphoproliferative
Solitary or extramedullary
3% (951)
2% (656)
Amyloidosis
Macro 2% (699)
(AL) 9% (2,815)
Other 2% (699)
Multiple
myeloma
17% (5,439)
MGUS
61% (19,042)
CP1102576-1
Monoclonal Gammopathies
Mayo Clinic 1960-2003 .
Osteosclerotic (POEMS)
139
0.4%
Plasma cell leukemia
75
heavy-chain disease
28
µ heavy-chain disease
2
Benign hypergammaglobulinemia
31
purpura of Waldenström (BHPW)
Light chain deposition disease
63
Acquired Fanconi syndrome
36
Cryoglobulinemia
227
0.7%
Scleromyxedema
23
Bence Jones Proteinuria
29
Cold agglutinin disease
46
Total
699
CP1102576-2
CRYOGLOBULINEMIA
· 66 Patients seen 3/2/94-11/30/00
· Only type II included
· Median age 58; M:F 36:30
· Cryocrit median 3.9% with 60/66
having cryocrit <10%
· 65 M 1 M (Serum IF in 51%)
· Rheumatoid Factor + 97%
TYPE II CRYOGLOBULINEMIA
PATIENT SYMPTOMS
60
50
40
% 30
20
10
0
Purpura
Renal
Edema
Neuropathy
Arthralgia
TYPE II CRYOGLOBULINEMIA
PATIENT UNDERLYING DISORDERS
70
60
50
40
%
30
20
10
0
HCV
LPD
Autoimm
"Essential"
CRYOGLOBULINEMIA
Clinical Associations
· Skin Ulceration more frequent in
patients with underlying LPD
· Neuropathy & Raynauds more
common in Autoimmune Patients
CRYOGLOBULINEMIA
Serum Protein Electrophoresis
70
60
50
40
30
20
10
0
Normal
Poly
Hypo
M-spike
M-
spike+poly
CRYOGLOBULINEMIA
Therapy & Survival
· Only 21% died, Only predictor of
survival Age
80
70
60
Response 50
Rate%
40
30
20
10
0
Interferon
Steroids
Cyclophos Rituximab
CRYOGLOBULINEMIA
Therapy & Survival
Response Rate based on Primary Indication for Rx
90
80
70
60
50
% 40
30
20
10
0
y
y
cers
ath
Skin
Kidne
Ul
urop
Ne
RESPONSE OF A CRYO ULCER
TO RITUXIMAB
A
B
C
D
POEMS
· Syndrome distinguished from MGUS
neuropathy
Sclerotic Bone Lesion (95%)
showing plasmacytoma if biopsied
Castleman Disease (11%)
· Clinical Clues Age 51 yr, Marrow
<10% PC's (86%), Platelets>450k 54%
PRESENTING SYMPTOMS IN
POEMS
100
90
80
70
60
50
40
30
20
100
Neu
O
M
T
P
r
h
o
rg
-s
r
ap
p
a
p
o
i
a
n
i
m
ll
t
k
e
h
o
e
b
d
y
meg
o
e
a
c
m
ly
ythe
a
mia
OVERALL SURVIAL OF PATIENTS WITH
POEMS
# of patients dying of myeloma =0
Dispenzieri, A. et al. Blood 2003;101:2496-2506
OVERALL SURVIAL OF PATIENTS WITH POEMS
Based on therapy given
Dispenzieri, A. et al. Blood
2003;101:2496-2506
P=0.04
CHARACTERISTICS OF
TRANSPLANTED POEMS PATIENTS
· Nine in Wheelchairs, Median age 51
· Median 3 prior therapies
· Symptoms to SCT 42 mo
· Diagnosis to SCT 5 mo
· Minimum CD34+ 3.3x106
· Three MEL 140, 12 MEL 200, 1 BEAM
· All , Median M spike 0.2
THERAPY MORBIDITY
· 37% ON VENTILATOR
· 1 DEATH Graft failure after acute
febrile illness
STEM CELL TRANSPLANTATION
FOR POEMS
Compound muscle action potential
Neuro impairment score
CONCLUSIONS
· Poems & Cryo are non fatal disorders.
The former almost always IgM with
rheumatoid activity, and features of
vasculitis the latter a dominant
process with polyneuropathy & a
sclerotic bone lesion. In POEMS stem
cell transplant is effective in
radiotherapy failures